Matrix Metalloproteinases (MMPs) are a class of metalloenzymes integral to embryonic development, morphogenesis, and the maintenance and remodeling of the extracellular matrix. However, MMP upregulation is also characteristic of tumor growth and metastasis, in particular, the gelatinases MMP-2 and MMP-9. Because of this, MMP inhibitors have been explored as promising antitumor targets. Separately, MMP inhibitor scaffolds have been used to target tumor cells. Currently, boron neutron capture therapy (BNCT) is experiencing a renaissance, as it ideally involves targeting tumors with cellular-precision. BNCT involves the irradiation of 10B atoms with low-energy thermal neutrons, giving rise to an excited 11B atoms which then undergo fission. The high energy products of 11B fission only travel ~1 μm on average, ~1/10 to 1/30 the diameter of a human cell. Therefore, only the cells immediately adjacent to the boron atoms undergoing fission receive lethal damage, while all other, nonadjacent cells remain unaffected. The efficacy of BNCT is reliant on two conditions: tissue-specific delivery of 10B atoms and achieving a sufficient tumor concentration of 10B-isotopes (20 µg/g). We hope to satisfy both of these conditions with hydroxamate MMP inhibitor 1, a sulfonamide-based MMP-inhibitor appended with an icosahedral carborane cluster. We will describe the successful synthesis of MMP inhibitor 1, based on known MMP inhibitor CGS-27023A, a potent stromelysin inhibitor with affinity for gelatinases MMP-2 and -9. Compound 1 is currently undergoing testing as a new BNCT agent.

Synthesis of a novel, MMP-inhibitor-based boron delivery agent for use in oncological boron neutron capture therapy (BNCT)

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.